摘要：There is mounting evidence that HAP1 is involved in intracellular trafficking. For example，HAP1 isknown to associate with microtubule-dependent transporters，variousmembrane receptors，and anumber of membranous organelles. One key question remainshow HAP1 is able to participate inthese diverse and distinct trafficking processes. HAP1 may act as a scaffold to stabilize proteincomplexes that are required for prot-ein trafficking. It could also function as an adaptor to linkmicrotubule transport-ers with different cargos. Ultimately，the regulation of HAP1 trafficking functionmight occur at multiple levels. Phosphorylation can influence the affinity of HAP1 for binding to itspartners. The 14-3-3 protein can also regulate the interaction ofHAP1 with trafficking proteins. SinceHAP1 exists as a heterodimer formed by the HAP-1A and HAP1B isoforms，the different sequences inthese isoforms could regulate thefunction and stability of HAP1 heterodimers. As discussed above,mutant htt can impair the function of HAP1 via increased binding to HAP1. Furthermore，differentlevelsof HAP1 and its partners in different cells may confer cell type-specific functions. For example,the abundant expression of HAP1 in the hypothalamic neurons could be important for the survival ofthese neurons，aside from its role in intracellular tr-afficking. In this regard，HAP1 conditionalknockout offers a powerful tool for exa-mining the cell type-specific functions of HAP1. The knockoutapproach can also be brought to bear on the key question of how dysfunction in HAP1-associatedtraffickin-g contributes to HD pathogenesis. A defect in BDNF transport，which requires both HAP1and htt，has been associated with HD pathogenesis. Since axonal transport of BD-NF in corticalneurons is critical for viability of the striatal neurons that are p-referentially affected in HD，it wouldbe interesting to investigate whether there is a defect in HAP1-associated transport in cortical neurons.Thus，further characterization of the cell type-specific function of HAP1 will help to elucidate theselec-tive vulnerability of these cells in HD.
